Malignant cells do not respond to the regulatory signals which control the proliferation of normal cells. Unfortunately, it is and will remain difficult to define the nature of the defect in malignant cells while so little is known concerning the control of cell division in normal cells. The object of this research is to expand our knowledge of cell division in both normal and malignant cells. In this proposal we plan to determine the role of differential gene function in human diploid cells as they undergo the transition from quiescence to the proliferative state and traverse the various periods of the cell cycle leading to cell division. The analysis of gene function will be based on the results of DNA-RNA hybridization studies utilizing the nonrepeated sequences of DNA. We will also determine whether malignant cells are characterized by an altered pattern of gene transcription and, if so, whether this reflects the activation of normally unexpressed late-replicating genes.